Ephrin receptor 8 is a protein encoded by a gene EPHA8 in humans. This gene encodes a member of the ephrin receptor subfamily of protein tyrosine kinases. In the central nervous system, EPH-related receptors EPH is involved in mediating a particular developmental event. Usually, EPH subfamily receptors, have an extracellular region containing two fibronectin type III repeats and cysteine-rich domain and kinase domain of the single. Are divided into two groups based on the similarity of their affinity for the ligand ephrin binding and ephrin-AB extracellular domain sequence of the ephrin receptor. Protein is encoded by a gene that functions as a receptor for A5 and A2, A3 ephrins, play a role in short-range contact-mediated axonal guidance during development of the mammalian nervous system.
This gene encodes a member of the ephrin receptor subfamily of protein tyrosine kinases. In the central nervous system, EPH-related receptors EPH is involved in mediating a particular developmental event. Usually, EPH subfamily receptors, have an extracellular region containing two fibronectin type III repeats and cysteine-rich domain and kinase domain of the single. Are divided into two groups based on the similarity of their affinity for the ligand ephrin binding and ephrin-AB extracellular domain sequence of the ephrin receptor. Protein is encoded by a gene that functions as a receptor for A5 and A2, A3 ephrins, play a role in short-range contact-mediated axonal guidance during development of the mammalian nervous system.
Effects related receptor and ephrin ligands they are stored in the family of proteins that play an important role in inducing cell migration and very axons. This study was to examine the major phosphorylation site of the two, the functional role of Tyr-838 of EphA8 receptor tyrosine -615. Phosphorylated peptide mapping analysis of two-dimensional, tyrosine – showed that tyrosine 838 and -615 is the major phosphorylation site in EphA8. Suggesting that phosphorylation has a physiological role, -615 tyrosine is phosphorylated to stoichiometry of the best on this site. In the domain of tyrosine kinase mutations conservative Tyr-838 at the time, the catalytic activity of EphA8 is significantly decreased in both in vivo and in vitro, the membrane domain in the vicinity of Tyr-615 mutation of one It is not harmful to the tyrosine kinases. not the SH2 domain preferential binding pair Fyn, phosphorylation of Tyr-615 in EphA8 has been shown to mediate-SH2 domain (GAP in Ras) GTP GTPase-activating protein for Ras and Src in in vitro binding studies . Shows a high EphA8 Fyn that EphA8 found in, and further immunoprecipitation the foehn in intact cells can be physically, to associate in vivo. It is significantly reduced Unlike association of mutant Fyn functions including EphA8 in both the 838 or -615 of Tyr-Tyr of. Tyrosine phosphorylation of tyrosine -615, these data phosphorylation efficient Tyr-615 of the show that integrity one 838 phosphorylation is important in order to determine the relationship between Fyn, and is required for significant other objects. Finally, the attenuation, cell response is Tyr phosphorylation or by signing over-expression of wild-type EphA8 receptor – that is the degree much lower than EphA8 mutant lacking tyrosine 838 or -615 were observed. In addition, transient expression of the kinase inactive Fyn, by reducing the signaling EphA8 the pin, has been blocked the cellular response in cells expressing excess EphA8 over. We Fu~yukinaze is one of the chain EphA8 signaling pathways of the main objectives that lead to changes in cell adhesion, why autophosphorylation and tyrosine -838 provides is important for positive regulation of signaling the EphA8 event is.
Recent studies that the gene is functional in Eph receptor pathway Ephrin-independent kinase has been shown. You will report that the expression of EphA8 increases the cell adhesion to fibronectin through β3integrins or α5β1 in both HEK293 cells or NIH 3T3. Interestingly, kinase inactive mutant EphA8, increased binding cells to fibronectin in these cell lines substantially. Use of a composition of EphA8 point mutant, EphA8 kinase activity has been shown that it is not correlated with the ability to promote cell attachment fibronectin we. Analyses EphA8 outside and with the intracellular domain mutants, the cell adhesion enhanced to be dependent on binding to cytoplasmic segment juxtamembrane domain of the receptor and the extracellular domain ephrin revealed. Is inhibited by – (kinase PI 3) kinase inhibitor – wortmannin, phosphatidylinositol 3 effectively EphA8 promote adhesion. In addition, 3 PI is EphA8 we – As a result of the kinase activity, the p110γ isoform of PI, 3 – binding experiments in the discovery vitro, EphA8 juxtamembrane segment is stable and p110γ that the kinase is associated with the EphA8 I revealed that it is sufficient to form a complex. Obtained in assays using cells lacking the ligand ephrin endogenous by treatment with protein preclustered ephrin A5-Fc similar results. Furthermore, it indicates that it is associated stably membrane targeting lipid kinase inactive mutant p110γ, is suppressed EphA8 EphA8 promotion to fibronectin, cell attachment. Taken together, these results, in order to enable the signals required for thereby that it provides access to the lipid substrate to localize EphA8p110γPI-3 kinase in the cell membrane receptor tyrosine kinase-dependent manner integrin-mediated cell adhesion, indicating that a new mechanism exists by.
In the contact-dependent bidirectional signaling device to adjacent cells, and as a result, random GPI-anchored ephrin present in the cell in the adjacent – receptor tyrosine kinase that binds the family ligand. Downstream between signaling pathways ligand ephrin reverse signaling is called downstream signaling the first signaling path of the receptor. EFNA5 that can be EPHA8 the activation GPI-anchored ephrin-EFNA2, EFNA3 by phosphorylation. Migration to fibronectin substrates and integrin-mediated cell adhesion and EFNA5, however, you can adjust the neurite outgrowth. I have played a role in axon guidance and development of the nervous system. Contains the EPHA8 FYN promote the activation and cell adhesion of EPHA8 MAP kinase stimulates neurite outgrowth effector of downstream signaling pathways.
Four hetero ligand binding. I consists of ephrin receptor dimer and tetramer hetero. Oligomerization, it is necessary to induce a biological response probably. Further it is possible to form heterodimers and ephrin receptors other. And interact with FYN; possible effector of EPHA8 in the regulation of cell Traction. I regulate the integrin-mediated cell adhesion to the substrate; react with PIK3CG. I adjust the clathrin-dependent endocytosis of EPHA8; dialogue with TIAM1. EPHA8 kinase-independent; interact with ANKS1B and ANKS1A However, stimulated by EPHA8 ubiquitination.